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Disruption of Tacc3 function leads to in vivo tumor regression

R Yao1, Y Natsume, Y Saiki

  • 1Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo, Japan. ryao@jfcr.or.jp

Oncogene
|June 21, 2011
PubMed

Insights

Transforming acidic coiled-coil-3 (Tacc3) is a promising cancer target. Loss of Tacc3 caused lymphoma regression and apoptosis in mice, with no harm to normal tissues, highlighting its potential in chemotherapy.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Accurate chromosomal segregation during mitosis relies on bipolar spindle formation.
  • Microtubule dynamic instability is crucial for mitosis and a target for cancer chemotherapy.
  • Existing drugs targeting mitotic proteins like Eg5, Aurora kinases, and Polo-like kinases show limited efficacy, necessitating new targets.

Purpose of the Study:

  • To investigate transforming acidic coiled-coil-3 (Tacc3) as a novel molecular target for cancer chemotherapy.
  • To evaluate the in vivo effects of Tacc3 loss on lymphoma regression and normal tissue toxicity.

Main Methods:

  • In vivo studies using MRI to assess tumor regression following Tacc3 loss in mouse thymic lymphoma.
  • In vitro analysis of Tacc3 depletion effects on spindle formation, mitotic progression, and apoptosis.
  • Assessment of Tacc3 expression in normal tissues.

Main Results:

  • Tacc3 loss induced regression of mouse thymic lymphoma, accompanied by significant apoptosis.
  • Normal tissues, including the thymus, exhibited no abnormalities despite high Tacc3 expression.
  • In vitro, Tacc3 depletion led to multi-polar spindle formation, mitotic arrest, and subsequent apoptosis in lymphoma cells.
  • Similar effects were observed in Burkitt's lymphoma and T-ALL models.

Conclusions:

  • Tacc3 is a vulnerable component of the spindle assembly in lymphoma cells.
  • Tacc3 represents a promising and specific therapeutic target for cancer chemotherapy, particularly for lymphomas.
  • Targeting Tacc3 offers a potential strategy with minimal toxicity to normal tissues.

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